Histone Acetyltransferases: Targets and Inhibitors

Among the other posttranslational modifications, protein acetylation has been identified as one of the key mechanisms in the regulation of biological functions. Acetylation is a dynamic process that involves the transfer or removal of acetyl groups to ϵ‐amino group of lysine residues and is mediated by acetyltransferase and deacetylase enzymes, respectively. Lysine acetyltransferase (KAT) enzymes could be classified using different classifications on the basis of their subcellular localization or on the basis of their structural homology and/or catalytic mechanism. The general control non‐repressible 5‐related N‐acetyltransferase (GNAT) family is evolutionarily conserved from bacteria to mammals. KAT2A is an example for substrate discrimination by the structural motifs that are a typical feature of GNAT family. More commonly referred to as Hat1, KAT1 is a cytoplasmic KAT enzyme that acetylates newly synthesized free histones during chromatin assembly. One of the hypotheses to explain the mechanism underlying the acetylation of mitochondrial proteins is the existence of mitochondrial acetyltransferases.